A number of proteolytic enzymes such as elastase and collagenase have been shown to be involved in diseases such as pulmonary emphysema which involve tissue destruction. The goal of this proposed research is to design and synthesize specific and effective inhibitors for these proteolytic enzymes. The inhibitors will be tested for effectiveness and specificity with a variety of enzymes. Work with human leukocyte elastase and collagenase will be stressed. The inhibitors should be invaluable in the study of the normal biological function and the role of these proteases in disease. Synthetic protease inhibitors should find use in the clinical treatment of pulmonary emphysema, rheumatoid arthritis and other diseases. In addition, inhibitors may be invaluable in the protection from lung disease of individuals with low levels of alpha 1-antitrypsin, and other high risk populations. BIBLIOGRAPHIC REFERENCE: "Reaction of Acyl Carbazates with Proteolytic Enzymes," J. C. Powers and D. L. Carroll, Biochem. Biophys. Res. Comm., 67, 639 (1975).